丙氨酸氨基转移酶正常或轻度升高的慢性乙型肝炎患者抗病毒疗效的影响因素

doi:10.3877/cma.j.issn.1674-1358.2016.04.007

中华实验和临床感染病杂志(电子版) ›› 2016, Vol. 10 ›› Issue (04) : 417 -421. doi: 10.3877/cma.j.issn.1674-1358.2016.04.007

临床论著

丙氨酸氨基转移酶正常或轻度升高的慢性乙型肝炎患者抗病毒疗效的影响因素

欧蔚妮¹, 张娜², 王笑梅¹, 杨松¹, 成军¹, 邢卉春¹^,^†(

), 程丹颖¹, 段英¹, 刘庄¹, 赵莹莹¹

^1. 100015　北京，首都医科大学附属北京地坛医院肝病中心
^2. 261000　潍坊，潍坊市人民医院感染病科

收稿日期:2015-08-28 出版日期:2016-08-15
通信作者: 邢卉春
基金资助:
北京市卫生系统高层次卫生技术人才培养计划(No. 2015-3-108); 首都卫生发展科研专项项目(No.首发2011-2017-02); 首都卫生发展科研专项项目(No.首发2014-2-2172)

The related factors of antiviral response in ALT normal or mild elevated patients with chronic hepatitis B

Weini Ou¹, Na Zhang², Xiaomei Wang¹, Song Yang¹, Jun Cheng¹, Huichun Xing¹^,^†(), Danying Cheng¹, Ying Duan¹, Zhuang Liu¹, Yingying Zhao¹

^1. Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
^2. Department of Infectous Diseases, The People’s Hospital of Weifang City, Weifang 261000, China

Received:2015-08-28 Published:2016-08-15
Corresponding author: Huichun Xing

全文 ( ) 下载PDF ( ) 导出引用

引用本文：

欧蔚妮, 张娜, 王笑梅, 杨松, 成军, 邢卉春, 程丹颖, 段英, 刘庄, 赵莹莹. 丙氨酸氨基转移酶正常或轻度升高的慢性乙型肝炎患者抗病毒疗效的影响因素[J]. 中华实验和临床感染病杂志(电子版), 2016, 10(04): 417-421.

Weini Ou, Na Zhang, Xiaomei Wang, Song Yang, Jun Cheng, Huichun Xing, Danying Cheng, Ying Duan, Zhuang Liu, Yingying Zhao. The related factors of antiviral response in ALT normal or mild elevated patients with chronic hepatitis B[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2016, 10(04): 417-421.

目的

探讨肝组织学、丙氨酸氨基转移酶（ALT）等因素与慢性乙型肝炎抗病毒疗效的相关性。

方法

回顾性分析首都医科大学附属北京地坛医院2005至2010年住院行肝组织活检后抗病毒治疗的慢性HBV感染者共81例，采集患者抗病毒治疗基线人口学、生化学、病毒学及肝组织学结果并收集患者抗病毒治疗随访过程中病毒学指标动态下降情况，分析此类患者抗病毒治疗应答相关因素。

结果

共纳入患者81例，其中男性60例；平均年龄36.5岁。肝组织学活检提示，肝脏炎症和纤维化≥ G2S2者54例（66.7%）；肝脏炎症和纤维化< G2S2者27例（33.3%）；治疗24周病毒学应答患者63例（77.8%）。肝组织学炎症或纤维化等级、ALT水平及患者平均年龄在抗病毒治疗应答组与无应答组差异均具有统计学意义（P均<0.05）。抗病毒药物类型[干扰素/核苷（酸）类似物]与患者病毒学应答无显著相关。

结论

ALT持续正常或轻度异常（< 2 × ULN）的慢性乙型肝炎患者抗病毒疗效与患者肝组织学炎症/纤维化程度及ALT水平显著相关，建议此类患者行肝组织活检以评价抗病毒指征及预测抗病毒疗效。

关键词: 丙氨酸氨基转移酶, 肝组织学, 肝炎, 乙型, 慢性

Objective

To investigate the relationship among liver histology features, alanine aminotransferase (ALT) level or other factors with the effect of antiviral treatment for patients with chronic hepatitis B (CHB).

Methods

Total of 81 cases with CHB who accepted liver biopsy in Beijing Ditan Hospital, Capital Medical University from 2005 to 2010 were analyzed, respectively. The baseline demographic for antiviral therapy, results of biochemistry, viral and liver histology were collected, meanwhile with the dynamic decline of indicators of viral during the follow-up process and the possible related factors of antiviral response were also analyzed.

Results

Among the 81 patients, there were 60 males, with the mean age of 36.5 years old. Liver inflammation and fibrosis of these patients were detected. There were 54 cases (66.7%) with liver inflammation and fibrosis ≥ G2S2, and 27 cases (33.3%) were < G2S2. There were 63 cases (77.8%) with 24 weeks of treatment achieved viral response. There were significant differences on the degree of liver inflammation, fibrosis ALT levels and average ages between the CHB patients who received antiviral treatment and had better virological response and with poor virological response (P all < 0.05). While there were no significant differences between the types of antiviral treatment [interferon (IFN) vs nucleoside (acid) analogue] of the patients with CHB virological response.

Conclusions

Antiviral treatment effect of CHB patients with persistently normal or mildly abnormal ALT level (< 2 × ULN) were significantly correlated with the levels of ALT in patients with liver fibrosis and the degree of liver inflammation and fibrosis, so the patients with persistently normal or mildly abnormal ALT level (< 2 × ULN) were advised to accept liver biopsy to evaluate antiviral condictions and effects.

Key words: Alanine aminotransferase, Liver pathology, Chronic hepatitis B

表1 不同肝脏病理状态患者抗病毒治疗病毒学应答情况

疗效	< G2S2 [例（%）]	≥ G2或≥ S2 [例（%）]	合计
应答佳	16（59.3）	47（87.0）	63
应答不佳	11（40.7）	7（13.0）	28
合计	27	54	81

表1 不同肝脏病理状态患者抗病毒治疗病毒学应答情况

疗效	< G2S2 [例（%）]	≥ G2或≥ S2 [例（%）]	合计
应答佳	16（59.3）	47（87.0）	63
应答不佳	11（40.7）	7（13.0）	28
合计	27	54	81

表2 不同肝脏病理状态与ALT水平患者抗病毒治疗病毒学应答情况[例（%）]

疗效	肝脏炎症和纤维化< G2S2		肝脏炎症和纤维化≥ G2S2
疗效	ALT正常	ALT轻度异常	ALT正常	ALT轻度异常
应答佳	4（57.1）	11（73.3）	11（78.6）	41（83.7）
应答不佳	3（42.9）	4（26.7）	3（21.4）	8（16.3）

表2 不同肝脏病理状态与ALT水平患者抗病毒治疗病毒学应答情况[例（%）]

疗效	肝脏炎症和纤维化< G2S2		肝脏炎症和纤维化≥ G2S2
疗效	ALT正常	ALT轻度异常	ALT正常	ALT轻度异常
应答佳	4（57.1）	11（73.3）	11（78.6）	41（83.7）
应答不佳	3（42.9）	4（26.7）	3（21.4）	8（16.3）

1	中华医学会肝病学分会，中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015更新版)[J]. 中华肝脏病杂志,2015,23(12):888-905.
2	Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors[J]. J Hepatol,2008,48(2):335-352.
3	参加慢性乙型肝炎长期治疗讨论会专家. 核苷和核苷酸类药物治疗慢性乙型肝炎的长期性[J]. 中华肝脏病杂志,2014,22(12):884-890.
4	Gong X, Yang J, Tang J, et al. A mechanistic assessment of the discordance between normal serum alanine aminotransferase levels and altered liver Histology in chronic hepatitis B[J]. PLoS One,2015,10(7):e0134532.
5	Du X, Wang J, Shao L, et al. Histological improvement of long-term antiviral therapy in chronic hepatitis B patients with persistently normalalanine aminotransferase levels[J]. J Viral Hepat,2013,20(5):328-335.
6	Papachrysos N, Hytiroglou P, Papalavrentios L, et al. Antiviral therapy leads to histological improvement of HBeAg-negative chronic hepatitis B patients[J]. Ann Gastroenterol,2015,28(3):374-378.
7	陈永鹏，汪艳，侯金林. 肝纤维化/肝硬化的动态变化及其诊断进展[J]. 中华肝脏病杂志,2015.4(23)4:244-246]。
8	张娜，赵莹莹，欧蔚妮, 等. 肝功能正常或轻度异常的慢性HBV感染者肝组织病理改变分析[J/CD]. 中华实验和临床感染病杂志:电子版,2014,8(1):17-21.
9	耿晓霞，林健梅，杨兴祥, 等. 慢性乙型肝炎病毒携带者和ALT轻度升高慢性乙型肝炎患者的肝脏病理及临床特征[J]. 中华肝脏病杂志,2009,17(10):735-739.
10	杨兴祥，江南，黄仁刚, 等. 慢性乙型肝炎丙氨酸转氨酶低于2倍正常上限者的肝组织学改变[J]. 中华消化杂志,2011,31(9):594-597.
11	Wang H, Xue L, Yan R, et al. Comparison of histologic characteristics of Chinese chronic hepatitis B patients with persistently normal ormildly elevated ALT[J]. PLoS One,2013,8(11):e80585.
12	Zheng X, Wang J, Yang D. Antiviral therapy for chronic hepatitis B in China[J]. Med Microbiol Immunol,2015,204(1):115-120.
13	Alam MM, Mahtab MA, Akbar SM, et al. Hepatic necroinflammation and severe liver fibrosis in patients with chronic hepatitis B with undetectable HBV DNA and persistently normal alanine aminotransferase[J]. Bangladesh Med Res Counc Bull,2014,40(3):92-96.
14	刘顺庆，朱晓骏，孙学华, 等. ALT轻度升高的HBeAg阳性和阴性慢性乙型肝炎患者肝组织病理学特点[J]. 中华肝脏病杂志,2012,20(5):348-352.
15	应若素，杨湛，陈燕宇, 等. 丙氨酸氨基转移酶水平正常与轻度升高慢性HBV感染者的肝脏病理学特征比较[J]. 中华肝脏杂志,2012,20(8):585-588.
16	吴泽倩，谭雷，刘婷, 等. HBeAg阴性慢性乙型肝炎患者血清HBsAg水平在不同肝组织炎症分级和纤维化分期的变化[J]. 中华肝脏病杂志,2014,22(12):895-899.
17	Chan HL, Chan CK, Hui AJ, et al. Effects of tenofovir disoproxil fumarate in hepatitis B e antigen-positive patients with normal levels of alanine aminotransferase and high levels of hepatitis B virus DNA[J]. Gastroenterology,2014,146(5):1240-1248.
18	Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B[J]. N Engl J Med,2006,354(10):1001-1010.
19	Kim V, Abreu RM, Nakagawa DM, et al. Pegylated interferon alfa for chronic hepatitis B: systematic review and meta-analysis[J]. J Viral Hepat,2016,23(3):154-169.
20	Tang CM, Yau TO, Yu J. Management of chronic hepatitis B infection: current treatment guidelines, challenges, and new developments[J]. World J Gastroenterol,2014,20(20):6262-6278.
21	European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection[J]. J Hepatol,2012,57(1):167-185.
22	Liaw YF, Gane E, Leung N, et al. 2-year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B[J]. Gastroenterology,2009,136(2):486-495.
23	颜成果，姚云清，毛晓琴. 恩替卡韦治疗慢性乙型肝炎病毒携带者近期疗效观察[J]. 中华肝脏病杂志,2014,22(12):900-903.
24	Hadziyannis SJ, Vassilopoulos D, Hadziyannis E. The natural course of chronic hepatitis B virus infection and its management[J]. Adv Pharmacol,2013,67:247-291.
25	Chang TT, Gish RG, de Man R, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B[J]. N Engl J Med,2006,354(10):1001-1010.

[1]	高建松, 陈晓晓, 冯婷, 包剑锋, 魏淑芳, 潘林. 基于超声瞬时弹性成像的多参数决策树模型评估慢性乙型肝炎患者肝纤维化等级[J]. 中华医学超声杂志（电子版）, 2023, 20(09): 923-929.
[2]	王鹏, 肖厚安, 贾赤宇. 不同因素调控巨噬细胞极化在慢性难愈性创面中的研究进展[J]. 中华损伤与修复杂志(电子版), 2023, 18(05): 454-459.
[3]	韩春茂. 解决慢性创面患者医疗服务最后一公里[J]. 中华损伤与修复杂志(电子版), 2023, 18(05): 460-460.
[4]	李兆明, 章颖, 刘先进. 血小板计数、红细胞分布宽度对急性戊型肝炎肝衰竭患者预后的预测价值[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(05): 307-314.
[5]	张小曼, 马筱秋, 许正锯, 张纯瑜, 何彩婷. 乙型肝炎病毒逆转录酶区耐药突变对血清乙型肝炎病毒表面抗原水平的影响[J]. 中华实验和临床感染病杂志(电子版), 2023, 17(05): 324-332.
[6]	张潇尹, 于洋. 牙龈卟啉单胞菌介导慢性肾病发生发展的研究进展[J]. 中华口腔医学研究杂志(电子版), 2023, 17(05): 328-334.
[7]	吴方园, 孙霞, 林昌锋, 张震生. HBV相关肝硬化合并急性上消化道出血的危险因素分析[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 45-47.
[8]	范铁艳, 李君, 陈虹. 肝移植术后新发戊型病毒性肝炎的诊治经验[J]. 中华移植杂志(电子版), 2023, 17(05): 293-296.
[9]	周川鹏, 杨浩, 魏微阳, 王奇, 黄亚强. 微创与标准通道经皮肾镜治疗肾结石合并肾功能不全的对比研究[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(05): 470-475.
[10]	陈淑钿, 梁韵, 廖媛, 王杨. 补体C3在HBV相关慢加急性肝衰竭患者预后评估中的价值[J]. 中华肝脏外科手术学电子杂志, 2023, 12(05): 562-566.
[11]	何吉鑫, 杨燕妮, 王继伟, 李建国, 谢铭. 肠道菌群及肠道代谢产物参与慢性便秘发生机制的研究进展[J]. 中华结直肠疾病电子杂志, 2023, 12(06): 495-499.
[12]	易成, 韦伟, 赵宇亮. 急性肾脏病的概念沿革[J]. 中华临床医师杂志(电子版), 2023, 17(08): 906-910.
[13]	周婷, 孙培培, 张二明, 安欣华, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病诊断现状调查[J]. 中华临床医师杂志(电子版), 2023, 17(07): 790-797.
[14]	孔凡彪, 杨建荣. 肝脏基础疾病与结直肠癌肝转移之间关系的研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(07): 818-822.
[15]	孙培培, 张二明, 时延伟, 赵春燕, 宋萍萍, 张硕, 张克, 周玉娇, 赵璨, 闫维, 吴蓉菊, 宋丽萍, 郭伟安, 马石头, 安欣华, 包曹歆, 向平超. 北京市石景山区40岁及以上居民慢性阻塞性肺疾病患病情况及相关危险因素分析[J]. 中华临床医师杂志(电子版), 2023, 17(06): 711-719.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

The related factors of antiviral response in ALT normal or mild elevated patients with chronic hepatitis B

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

The related factors of antiviral response in ALT normal or mild elevated patients with chronic hepatitis B